Molecular mechanisms of methylsulfonylmethane and allicin in the inhibition of CD44 ± breast cancer cells growth

Sarkhani, Elham; Najafzadeh, Nowruz; Tata, Nasrin; Dastan, Maryam; Mazani, Mohammad; Arzanlou, Mohsen

doi:10.1016/j.jff.2017.10.007

Cited by 12 publications

(11 citation statements)

References 41 publications

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“…Other important pathways that regulate cell death are the anti-apoptotic y pro-apoptotic molecules, in this sense, it was shown that allicin induces apoptosis in breast tumor-initiating MCF-7 CD44 + cells by caspase-3, BAX1, and p53 pathways [34]. This is consistent with our findings that allicin treatment induced caspase-3, caspase-8, caspase-9 activation, and loss of DΨm, along with pro-apoptotic gene regulation.…”

Section: Discussionsupporting

confidence: 92%

Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple‐negative breast cancer: Caspase, ΔΨm, and pro‐apoptotic gene involvement

Rosas‐González

Téllez‐Bañuelos²,

Hernández‐Flores

et al. 2020

Fundamemntal Clinical Pharma

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Breast cancer is the most frequent cancer in women worldwide, and drug resistance is common in all breast cancer types. The combination of natural products with chemotherapies has attracted attention, as it was found that natural compounds enhance the effects of standard cancer chemotherapeutic drugs and protect from side effects. Into the different natural products, garlic has been recognized for its antitumor properties. It is suggested that its anticancer effects are associated with its organo‐sulfur compounds, especially alliin and allicin. Here, we evaluated the effects of both molecules on cell death, senescence, and their senolytic potential in luminal A and triple‐negative breast cancer cells. MCF‐7 (luminal A) and HCC‐70 (triple‐negative) cells were cultured and treated with different concentrations of alliin or allicin. Then, cell viability was determined using the WST‐1 reagent. Apoptosis and caspase activity were evaluated by flow cytometry; ΔΨm was assessed using a JC‐10 fluorometric assay kit. Apoptosis‐related genes were evaluated by RT‐PCR. Proliferation was measured using bromodeoxyuridine incorporation. We also evaluated clonogenicity, senescence (β‐Galactosidase Staining), and the senolytic effect of the compounds. Our results showed that allicin has antiproliferative, anticlonogenic, and senolytic effects. In addition, allicin decreased cell viability and induced apoptosis by loss of ΔΨm, caspase‐3, caspase‐8, and caspase‐9 activation, upregulation of NOXA, P21, and BAK, as well as downregulation of BCL‐XL expression. Contrary to allicin, alliin promoted clonogenicity, induced senescence, and did not exhibit pro‐apoptotic effects in breast cancer cells.

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Section: Discussionsupporting

confidence: 92%

Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple‐negative breast cancer: Caspase, ΔΨm, and pro‐apoptotic gene involvement

Rosas‐González

Téllez‐Bañuelos²,

Hernández‐Flores

et al. 2020

Fundamemntal Clinical Pharma

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“…Our results demonstrated that a combination of allicin and 5-FU effectively decreased the growth of 5-FU resistant gastric cancer which is consistent with studies of osteosarcoma [20], hepatocellular cancer cells [15], and neuroblastoma cells [13]. Previously, we also demonstrated that allicin in combination with methylsulfonylmethane increased apoptosis and inhibited cell cycle in CD44 ± breast cancer cells [21]. Jiang et al found that the combined treatment of allicin with artesunate decreases the viability of osteosarcoma cells and suppresses the metastasis and colony formation ability through the overexpression of caspase-3/9 [20].…”

Section: Discussionsupporting

confidence: 91%

Allicin Reduces 5-fluorouracil-resistance in Gastric Cancer Cells through Modulating MDR1, DKK1, and WNT5A Expression

et al. 2021

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Background & Objective 5-fluorouracil (5-FU) is approved for the treatment of gastric carcinoma (GC), but chemo-resistance limits the application of it for GC. Thus, the combination of 5-FU with adjuvants such as allicin may overcome multidrug resistance (MDR). Methods The anticancer effects of allicin, 5-FU, and allicin/5-FU on the 5-FU resistant MKN-45 cells were evaluated by MTT assay and DAPi staining. The expression of the P-glycoprotein (P-gp) and CD44 protein were determined using immunocytochemistry. We also quantified mRNA expression levels of WNT5A, Dickkopf-1 (DKK1), and MDR1 in the GC cells. Results Here, we found that the combination of allicin with 5-FU significantly increased apoptosis compared to 5-FU alone (P<0.05). We showed that WNT5A, MDR1, and DKK1 mRNA expression levels were down-regulated in the allicin- and allicin/5-FU-treated cells. Indeed, the combination of allicin and 5-FU significantly decreased the expression of the P-gp and CD44 proteins (P<0.05). Conclusion Our findings indicate that the combination of allicin with 5-FU could reverse multidrug resistance in the GC cells by reducing the expression of WNT5A, DKK1, MDR1, P-gp, and CD44 levels.

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“…Allicin (purity ≥ 95%) was purified from crushed garlic using the semi-preparative HPLC method, as described previously. 24 β-CD and ε-PL were purchased from the Sigma Chemical Company. DOX hydrochloride (DOX•HCl) was purchased from Beijing Huafeng United Technology Co., Ltd. Hepatic carcinoma cell line (HepG2) was purchased from American Type Culture Collection.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Self-Assembling Cyclodextrin-Based Nanoparticles Enhance the Cellular Delivery of Hydrophobic Allicin

Li²,

et al. 2020

J. Agric. Food Chem.

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Most chemotherapeutics are hydrophobic molecules and need to be converted into hydrophilic formulations before administration. To address this issue, a novel cyclodextrin-based nanoparticle was proposed as a versatile carrier for cellular delivery of hydrophobic molecules. First, the effect of the polylysine (PL)/NH2-β-cyclodextrin (NH2-β-CD) ratio on particle size and encapsulation efficiency in prepared complexes was investigated. Subsequently, transmission electron microscopy images showed that the sizes of PL/NH2-β-CD nanoparticles ranging from 10 to 260 nm decreased with the reduction in the PL/NH2-β-CD ratio, which was completely consistent with the findings of size distributions. At a PL/NH2-β-CD ratio of 10, the surface charge on the PL/NH2-β-CD nanoparticle was maximized at (+52.8 mV), and encapsulation efficiency was optimal (47.2%), which revealed a great advantage in delivery of hydrophobic allicin. In addition, the positive charge of PL chains facilitated the cellular uptake of the PL/NH2-β-CD-DOX by interacting with the negatively charged cell membrane. Conclusively, this study suggests that the combination of allicin and PL/NH2-β-CD nanoparticles acting on the S and G2/M phases in cell cycle regulation induces apoptosis and exhibits substantial application in killing cancer cells.

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Molecular mechanisms of methylsulfonylmethane and allicin in the inhibition of CD44 ± breast cancer cells growth

Cited by 12 publications

References 41 publications

Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple‐negative breast cancer: Caspase, ΔΨm, and pro‐apoptotic gene involvement

Differential effects of alliin and allicin on apoptosis and senescence in luminal A and triple‐negative breast cancer: Caspase, ΔΨm, and pro‐apoptotic gene involvement

Allicin Reduces 5-fluorouracil-resistance in Gastric Cancer Cells through Modulating MDR1, DKK1, and WNT5A Expression

Self-Assembling Cyclodextrin-Based Nanoparticles Enhance the Cellular Delivery of Hydrophobic Allicin

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